Department of Physiology, Marmara University School of Medicine, Basıbüyük Mah. Maltepe Basıbüyük Yolu No. 9/1, Istanbul, Maltepe, 34854, Türkiye.
Student at Marmara University School of Medicine, İstanbul, Türkiye.
BMC Neurosci. 2024 Aug 5;25(1):36. doi: 10.1186/s12868-024-00884-x.
Status epilepticus is a common and potentially life-threatening neurological emergency with a high risk for cognitive and neurobiological impairment. Our aim was to evaluate the neuroprotective effects of centrally administered irisin and acute exhausting exercise against oxidative brain injury and memory dysfunction due to a pentylenetetrazole (PTZ)-induced single seizure. Male Sprague Dawley rats with intracerebroventricular (icv) cannulas were randomly divided into intraperitoneally (ip) saline-injected control and PTZ-injected (45 mg/kg) seizure groups. Both the control and PTZ groups were then treated with irisin (7.5 µg/kg, 2 µl, icv), saline (2 µl, icv) or were forced to an acute bout of strenuous exercise before the ip injection of saline (control) or PTZ. Seizures were evaluated using the Racine score. To evaluate memory performance, a passive avoidance test was performed before and after PTZ injection. Following euthanasia at the 24th hour of seizure induction, brain tissues were removed for histopathological examination and for evaluating oxidative damage, antioxidant capacity, and neurotransmitter levels.
Glutamate/GABA imbalance observed in PTZ rats was corrected by irisin administration (p < 0.001/p < 0.01), while irisin prevented the generation of reactive oxygen species and lipid peroxidation (p < 0.05 - 0.001) and replenished the antioxidant catalase and glutathione levels (p < 0.01-0.01) in the cerebral tissue, and reduced the histologically evident neuronal injury due to a single seizure (p < 0.05 - 0.01). Irisin also delayed the onset of seizures (p < 0.05) and improved memory dysfunction (p < 0.05), but did not affect the severity of seizures. The acute exhaustive swimming exercise completed before PTZ-seizure depressed glutamate level (p < 0.001), maintained the oxidant/antioxidant balance, alleviated neuronal injury (p < 0.05 - 0.01) and upregulated cerebral BDNF expression (p < 0.05).
In conclusion, acute high-intensity exercise or exogenously administered irisin provides neuroprotection by maintaining the balance of excitatory/inhibitory neurotransmitters and oxidant/antioxidant systems.
癫痫持续状态是一种常见的、潜在危及生命的神经急症，具有认知和神经生物学损伤的高风险。我们的目的是评估中枢给予鸢尾素和急性剧烈运动对戊四氮（PTZ）诱导的单次发作引起的氧化脑损伤和记忆功能障碍的神经保护作用。雄性 Sprague Dawley 大鼠通过侧脑室（icv）套管随机分为腹腔内（ip）生理盐水注射对照组和 PTZ 注射（45mg/kg）癫痫发作组。对照组和 PTZ 组均给予鸢尾素（7.5µg/kg，2µl，icv）、生理盐水（2µl，icv）或在 ip 注射生理盐水（对照组）或 PTZ 前进行急性剧烈运动。使用 Racine 评分评估癫痫发作。为了评估记忆表现，在 PTZ 注射前后进行被动回避测试。在诱导癫痫发作后 24 小时处死时，取出脑组织进行组织病理学检查，并评估氧化损伤、抗氧化能力和神经递质水平。
PTZ 大鼠中观察到的谷氨酸/γ-氨基丁酸失衡通过给予鸢尾素得到纠正（p<0.001/p<0.01），而鸢尾素防止了活性氧和脂质过氧化的产生（p<0.05-0.001），并补充了抗氧化剂过氧化氢酶和谷胱甘肽水平（p<0.01-0.01）在脑组织中，并减少了单次发作引起的明显神经元损伤（p<0.05-0.01）。鸢尾素还延迟了癫痫发作的发作（p<0.05）并改善了记忆功能障碍（p<0.05），但不影响癫痫发作的严重程度。在 PTZ 癫痫发作前完成的急性剧烈游泳运动降低了谷氨酸水平（p<0.001），维持了氧化/抗氧化平衡，减轻了神经元损伤（p<0.05-0.01），并上调了脑源性神经营养因子表达（p<0.05）。
总之，急性高强度运动或外源性给予鸢尾素通过维持兴奋性/抑制性神经递质和氧化/抗氧化系统的平衡提供神经保护作用。
